The objective of the work described in this proposal is to apply our genetic selection procedure to facilitate rapid production of catalytic antibodies capable of cleaving any given peptide. The technology involves cotransformation of E. coli with a specially designed helper phage rendered infection incompetent together with a combinatorial library cloned into a phagemid. Only phagemids encoding catalytic antibodies of the desired specificity are packaged into infectious phage particles and thus readily recovered. This technology can be expected to obviate the need for design and synthesis of transition state analogs as well as the construction of separate libraries for each target peptide. Ultimately, these antibodies will serve as therapeutic agents for viral diseases. Catalytic antibodies selected by this procedure should provide a significant advantage over conventional monoclonal antibodies since each antibody can neutralize multiple targets, thus reducing the required dose. It should also be noted that this technology can be applied to the selection of human antibodies as easily as murine. PROPOSED COMMERCIAL APPLICATION: The genetic selection scheme described in this work will allow rapid selection of catalytic antibodies capable of cleaving any given protein with great specificity. Such antibodies would serve as therapeutics for viral diseases, allergy, and amyloidosis among other disease states. They would also serve as restriction proteases for research and industrial applications.